Most of the joints in the body represent synovial joints which have four distinguishing features: (1) the articulating surfaces of the bones are covered with hyaline cartilage called articulating cartilage; (2) the joint is enclosed by an articular capsule or joint capsule; (3) the inner layer of the joint capsule is lined with a thin vascular synovial membrane; and (4) the synovial membrane encloses a cavity into which a synovial fluid is secreted.
The causes of arthritis include trauma to a joint, bacterial infection and metabolic disorders.
Rheumatoid arthritis, the most important clinically, begins with inflammation of the synovial membrane; the inflammed synovial membrane produces an abnormal tissue known as pannus which grows over the articular cartilage. The articular cartilage is distorted and is occasionally destroyed. Current medications for arthritis include sodium aurothiomalate, penicillamine, antipyretic antiphlogistics such as aspirin and indomethacin, and corticosteroids. The severe pain caused by active arthritis can be temporarily relieved through the administration of hydrocortisone which shows a strong anti-inflammatory effect and also makes hyaluronic acid (hereinafter referred to as HA) in normal highly polymerized states. Corticosteroids are prescribed, even though, it is common knowledge for doctors to be cautious of the side effects like osteoporosis from a long-term prescription of corticosteroids.
The volume of abnormal HA in the synovial fluid increases in cases of infectious and rheumatoid arthritis. This abnormal HA is not properly polymerized and therefore can not maintain or improve joint function. If a properly polymerized HA could be introduced into the joint capsule, the treatment would be much more effective. From that point of view, a local injection of HA has recently been made available as an injection into the synovial cavity of osteoarthritis.
In the wound healing process following surgical operations beginning with the dissection of the skin, ineffective adhesion due to scars on each surgically traumatized organ may result and cause pain, mechanical ileus, functional disturbance, motor disturbance or orthopaedic impairment at the surgical region. These complications occur with the following steps: (1) surgical trauma to the organs; (2) inflammatory exudates, especially fibrin, are secreted on those tissues; (3) fibrino-fibrous inflammation on the tissues; (4) the fibrous strands on the organ contract; and (5) the complications occur.
Balazs et al. in Biology of the Fibroplast, pp. 237-252, Academic Press, London, 1973, reported in 1973 that HA inhibits cell migration and multiplication of certain cells in vitro. And it is speculated that HA influences the invasion and activity of cells participating in the acute and chronic inflammatory process and it is though to prevent fibrous tissue formation. However, it does not effectively suppress the formation of fibrin which is converted from excessive fibrinogen under a hypercoagulated condition.
At the same time, there are some reports that HA has a procoagulant activity. If this is true, the fibrin clot formation is to be promoted in areas having fibrinous inflammation like arthritis which may result in more severe ankylosis. Biological activities of implanted HA in the body are not well defined presently. It has not been proven that HA has an anti-inflammatory effect in biological inflammatory processes. It may cease the inflammation of osteoarthritis by improving the cushion effect and mechanical separation of tissues in the joint, not by relating to theoretical inflammation processes directly.
Even if HA indirectly effects the inflammation process, it does not effectively inhibit fibrous tissue formation, pannus nor ankylosis.
Implanted HA in the joint would temporarily be a physical barrier, not a biological inhibitor, for the invasion of exudates such as fibrin and inflammatory cells. Even though, it is considered that the implanted HA would mix with various inflammatory exudates under the mobility of the joint, and would be unable to inhibit the cell migration and fibrin clot formation in the synovial cavity.
LeBoeuf et al. in the "Journal of Biological Chemistry", Vol. 261, No. 27, pp. 12586-12592, 1986,"; reported in 1986 that human fibrinogen specifically binds hyaluronic acid in vitro, and suggested a close interaction between fibrin and HA. Moreover, excessive fibrinogen is more quickly converted to fibrin under the conditions of a depressed activity of plasminogen activator or lowered antithrombin concentrations which occur within the inflammed area.